MRI-guided therapeutic unit and methods

ABSTRACT

A high intensity focused ultrasound applicator includes a frame, ultrasonic emitters mounted on the frame and a bag containing a substantially air-free fluid permanently connected to the frame. The frame, the bag, the fluid within the bag and the emitters constitute a permanently connected unit which can be releasably connected to an ultrasonic actuation apparatus.

CROSS-REFERENCE TO RELATED APPLICATION

The present application is a divisional of U.S. patent application Ser.No. 09/083,414 filing date May 22, 1998 which claims benefit of U.S.Provisional Patent Applications 60/047,526, filed May 23, 1997;60/054,124, filed July 28, 1997; 60/062,518, filed Oct. 17, 1997;60/074,474, filed Feb. 12, 1998; and 60/075,324, filed Feb. 20, 1998.The disclosures of all of the aforesaid applications are incorporatedherein by reference.

FIELD OF THE INVENTION

The present invention relates to the art of intrabody therapy involvingapplication energy to the body and further relates to monitoring of suchtherapy by magnetic resonance.

BACKGROUND OF THE INVENTION

Various forms of therapy can be applied within the body of a human orother mammalian subject by applying energy from outside of the subject.In hyperthermia, ultrasonic or radio frequency energy is applied fromoutside of the subject's body to heat the tissues. The applied energycan be focused to a small spot within the body so as to heat the tissuesat such spot to a temperature sufficient to create a desiredtherepeautic effect. This technique can be used to selectively destroyunwanted tissue within the body. For example, tumors or other unwantedtissues can be destroyed by applying heat to heat the tissue to atemperature sufficient to kill the tissue, commonly to about 60° to 80°C., without destroying adjacent normal tissues. Such a process iscommonly referred to as “thermal ablation”. Other hyperthermiatreatments include selectively heating tissues so as to selectivelyactivate a drug or promote some other physiologic change in a selectedportion of the subject's body. Other therapies use the applied energy todestroy foreign objects or deposits within the body as, for example, inultrasonic lithotripsy.

Magnetic resonance is used in medical imaging for diagnostic purposes.In magnetic resonance imaging procedures, the region of the subject tobe imaged is subjected to a strong magnetic field. Radio frequencysignals are applied to the tissues of the subject within the imagingvolume. Under these conditions, atomic nuclei are excited by the appliedradio frequency signals and emit faint radio frequency signals, referredto herein as magnetic resonance signals. By applying appropriategradients in the magnetic field during the procedure, the magneticresonance signals can be obtained selectively from a limited region suchas a two-dimensional slice of the subject's tissue. The frequency andphase of the signals from different portions of the slice can be made tovary with position in the slice. Using known techniques, it is possibleto deconvolute the signals arising from different portions of the sliceand to deduce certain properties of the tissues at each point within theslice from the signals.

Various proposals have been advanced for using magnetic resonance tomonitor and guide application of energy within the body. As disclosed,for example, in the U.S. Pat. Nos.4,554,925, 4,620,546 4,951,688 and5,247,935, the disclosures of which are hereby incorporated by referenceherein, certain known magnetic resonance procedures are temperaturesensitive, so that magnetic resonance data acquired using theseprocedures will indicate changes in temperature of the tissues. Forexample, a magnetic resonance parameter referred to as T₁ orspin-lattice relaxation time will vary with temperature. If magneticresonance imaging apparatus is actuated to acquire T₁ for various volumeelements or “voxels” within the subject, the data for different voxelswill vary with temperature, at least within a tissue having generallythe same composition. The data can be portrayed as a visible image andhence different temperatures can be shown by the differences inbrightness or color within the displayed image. Thus, the locationwithin the body being heated can be monitored by monitoring such avisible image during application of energy to the body. Also, the degreeof the heating can be monitored by monitoring T₁ for the heated regions.Magnetic resonance parameters other than T₁ can be portrayed ormonitored in the same way.

Although these procedures have well been known, they have not beenwidely adopted in the medical community. Magnetic resonance imaginginstruments of the types commonly used for medical diagnosticapplications include large, precise magnets which are arranged to imposea high magnetic field, typically about one Tesla or more over arelatively large imaging volume typically 10 cm or more in diameter.Certain magnetic resonance imaging static field magnets severely limitaccess to the subject. For example, a solenoidal air-coresuperconducting magnet may have superconductive coils surrounding atubular subject-receiving space. The subject lies on a bed which isadvanced into the said tubular space so that the portion of the patientto be imaged is disposed inside of the tubular space. Iron core magnetstypically have ferromagnetic frames defining opposed poles and asubject-receiving space lying between the poles. Permanent magnets orelectromagnets are associated with the frame for providing the requiredmagnetic flux. Depending upon the design of the magnet, either thesuperconductive coils or the frame may obstruct access to the patientduring operation of the magnetic resonance instrument. Moreover, becausethe magnetic resonance imaging instruments typically employed inmedicine are expensive, fixed structures, there are substantial costsassociated with occupancy of the instrument. Because hyperthermiaprocedures typically require significant time to perform, it isexpensive to perform these procedures while the patient is occupying themagnetic resonance imaging instrument. Moreover, because instruments ofthis type are typically found only in specialized imaging centers andradiology departments of hospitals, use of the magnetic resonanceimaging instrument for therapeutic procedures is associated withconsiderable inconvenience to the patient and to the treating physician.Thus, despite all of the efforts devoted heretofore to MRI-guidedhyperthermia procedures and apparatus, there remains a considerable,unmet need for improvements in such procedures and apparatus which wouldreduce the cost and increase the convenience of such procedures.

Moreover, there has been a need for further improvement in hyperthermiaprocedures of this type. The physician typically aims the energyapplyingdevice manually and applies so-called “subthreshold” doses of energy,sufficient to heat the tissues slightly but insufficient to causepermanent change in the tissue. The physician then observes the locationof the heated spot on a magnetic resonance image to confirm that theenergy-applying device is aimed at the desired location in the subject'sbody.

The response of the tissues within the body to the applied energyvaries. Differences in tissue properties such as specific heat andthermal conductivity will cause differences in the change in thetemperature caused by absorption of a specific amount of energy. The“susceptibility” or tendency of the tissues to absorb the applied energyalso varies from place to place. Therefore, after the device has beenaimed onto a particular spot, the physician must apply a therapeuticdose by gradually increasing the amount of the energy applied to thespot and monitoring the degree of temperature change to the spot bymeans of the magnetic resonance information as, for example, byobserving the visually displayed magnetic resonance image.

Typically, the spot heated during each operation of the energyapplyingdevice is relatively small as, for example, a spot about 1 mm-3 mm indiameter. To treat a large region within the subject, the spot must berepositioned many times. All of this requires considerable time andeffort. Moreover, the procedure is subject to errors which can causedamage to adjacent organs. For example, thermal energy is commonlyapplied to treat benign prostatic hyperplasia or tumors of the prostategland. If the physician mistakenly aims the energyapplying device at theurethra and actuates it to apply a therapeutic dose, the delicatestructure of the urethra can be destroyed. Therefore, improvements inthermal energy treatments which improve the safety of such treatmentsand reduce the effort required to perform such treatments, would bedesirable.

SUMMARY OF THE INVENTION

The present invention addresses these needs.

One aspect of the present invention provides therapeutic apparatus.Apparatus according to this aspect of the invention desirably includes amovable static field magnet adapted to apply a static magnetic field ina magnetic resonance volume at a predetermined disposition relative tothe static field magnet and also includes an energy applicator adaptedto apply energy within an energy application zone at a predetermineddisposition relative to the applicator. Apparatus according to thisaspect of the invention also includes positioning means for moving thestatic field magnet and the energy applicator to position the magnet andthe applicator so that the magnetic resonance volume at least partiallyencompasses a region of the subject to be treated and so that the energyapplication zone associated with the applicator intersects the magneticresonance volume within the region of the subject to be treated.Preferably, the apparatus includes a chassis and both the static fieldmagnet and the energy applicator are mounted to the chassis. Thepositioning means in this case includes means for moving the chassis soas to position the chassis relative to the subject. The static fieldmagnet desirably is a single-sided static field magnet arranged so thatthe magnetic resonance volume is disposed outside of the static fieldmagnet and spaced from the static field magnet in a forward direction.The static field magnet most preferably is substantially smaller thanthe static field magnets utilized in conventional magnetic resonanceimaging instruments. For example, the static field magnet may havedimensions of a meter or less and may be light enough to be movedreadily by a positioning device of reasonable cost and proportions.Thus, the entire apparatus can be moved as required to position itadjacent to the region of the subject's body which requires treatment.The most preferred apparatus according to this aspect of the presentinvention is small enough and inexpensive enough to be used in aclinical setting such as a physician's office or medical center. Thus,it is feasible to perform magnetic resonance-monitored energy applyingprocedures in a normal clinical setting. There is no need to occupy anexpensive diagnostic magnetic resonance imaging instrument during suchprocedures.

Additional aspects of the present invention provide improvedsingle-sided static-field magnets for magnetic resonance. Even with suchimprovements, however, the small single-sided static field magnettypically is capable of providing a magnetic field suitable for magneticresonance imaging only in a relatively small magnetic resonance volumeas, for example, a magnetic resonance volume with dimensions of a fewcentimeters. Such a small imaging volume normally would be regarded asundesirable in an instrument for general purpose magnetic resonanceimaging purposes. However, instruments according to this aspect of thepresent invention incorporate the realization that energy-applyingprocedures are applied within relatively small regions of the subject'sanatomy, so that an instrument with a small magnetic resonance volumestill can provide useful information for controlling the energy-applyingprocedures. Moreover, the image quality which is required for control ofenergy application is less than that which is required in diagnostic MRIimaging. The use of a relatively small magnetic resonance volume thenpermits use of a single-sided magnet which is relatively small, lightweight and inexpensive.

Apparatus according to this aspect of the invention desirably alsoincludes ancillary equipment such as gradient coils for applying amagnetic field gradient within the magnetic resonance volume. Thegradient coils may be mounted to the chassis or otherwise secured inposition relative to the static field magnet. The apparatus may alsoinclude radio frequency equipment for applying radio frequency signalsto the subject and receiving the resulting magnetic resonance signals,as well as devices for actuating the gradient coils to apply the fieldgradients. The apparatus may further include a computer for processingthe magnetic resonance signals such as to derive an image of tissues ofthe subject within the magnetic resonance volume in working frame ofreference such as the local magnetic resonance frame of reference, theframe of reference of the static field magnet. The computer can alsoprocess the magnetic resonance signals to derive temperatures of tissuesof the subject at one or more locations in the working frame ofreference.

The energy applicator may include an array of ultrasound-emittingtransducers and may also include a flexible fluid container mountedbetween the ultrasound transducer array and the energy application zoneso that the flexible fluid container can be engaged between thetransducer array and a surface of the subject's body. In a particularlypreferred arrangement, the energy applicator includes a mounting and thearray of transducers and the flexible fluid container are provided as adisposable unit releasably coupled to the mounting. Stated another way,the permanent component of the apparatus may include, as the energyapplying device, a mounting suitable for receiving such a disposableunit. Typically, the mounting provides electrical connections for thetransducer array and also provides mechanical securement for thedisposable unit. In a particularly preferred arrangement, the apparatusincludes a radio frequency antenna in the form of a loop fortransmitting or receiving RF signals. The antenna is secured in positionto the mounting so that when the ultrasonic transducers array andflexible fluid container are secured to the mounting, the antennaencircles the flexible fluid container at or near the surface of thepatient's body. The static field magnet is typically arranged to providea magnetic field directed in an axial direction, along a central axis.Desirably, the energy applicator and RF antenna are positioned so thatan applicator axis extending from the applicator into the overlappingportions of the energy application volume and magnetic resonance volumeis transverse to the central axis of the static field magnet. The RFloop antenna axis is also transverse to the central axis of the staticfield magnets. As further discussed below, this arrangement isconvenient to use and also enhances the interaction between thetransmitted RF signals and the atomic nuclei in the imaging volume aswell as the signal to noise ratio of the received magnetic resonancesignals.

A further aspect of the invention provides magnetic resonance apparatus,in particular, imaging apparatus incorporating movable single-sidedstatic field magnets and positioning devices as discussed above.Magnetic resonance apparatus according to this aspect of the inventionmay serve as a component of the treatment apparatus as may also be usedindependently to provide images of regions in the subject for otherpurposes.

A further aspect of the present invention provides methods of treatingliving subjects, such as a human or other mammalian subject. Methodsaccording to this aspect of the invention include the steps ofpositioning a movable static field magnet adapted to apply a staticfield in a magnetic resonance volume, the magnet being positionedrelative to the subject so that the magnetic resonance volume at leastpartially encompasses a region of the subject to be treated. A movableapplicator adapted to apply energy within an energy application zone ispositioned relative to the subject so that the energy application zoneintersects the magnetic resonance volume within the region of thesubject requiring treatment. While the static field magnet is applyingthe static magnetic field in the magnetic resonance volume, radiofrequency signals are applied so as to elicit magnetic resonance signalsfrom tissues of the subject in the magnetic resonance volume. The methodfurther includes the step of receiving these magnetic resonance signalsand deriving magnetic resonance information relative to the subject'stissues in the magnetic resonance volume from the magnetic resonancesignals. Further, the method includes the step of actuating the movableenergy-applying device to apply energy to tissues of the patient in theenergy application zone so as to treat the tissues and controlling oneor more parameters of the treatment by use of the magnetic resonanceinformation.

As mentioned above in connection with the apparatus, the use of movablestatic field magnets and energy applicators allow these devices to bepositioned relative to the patient. Here again, it is preferred to use astatic field magnet and energy applicator which are mounted to a commonchassis, so that the positioning steps include the step of moving thechassis so as to position the chassis relative to the subject. Thechassis may be moved after the procedure so as to reposition themagnetic resonance volume and energy application zone in a new region ofthe subject and the remaining steps of the procedure may be repeated soas to treat the tissues in a new region. The methods according to thisaspect of the invention also include the realization that because thetreatment procedure is localized, it can be performed using a magnetwith a relatively small magnetic resonance volume.

Most preferably, the magnetic resonance signals are spatially encoded,and the step of deriving magnetic resonance information is performed soas to derive magnetic resonance information at one or more points withinthe magnetic resonance volume, the points having locations defined inthe local magnetic resonance frame of reference. The parameter orparameters of the treatment which are controlled using the magneticresonance information may include the location of the treated tissues.Thus, the monitoring step may include the step of controlling thelocation of the treated tissues in a working frame of reference which iscorrelated to the local magnetic resonance frame of reference. Thus, thestep of controlling the location of the treated tissue may include thestep of aiming the energy applicator so as to apply the energy at one ormore treatment locations having positions defined in the working frameof reference. The aiming procedure may involve either moving theapplicator or, in the case of a phased array applicator, adjusting thephases and amplitudes of the signals supplied to the elements of thearray. The method may further include the step of displaying an image ofthe subject's tissues in a working frame of reference, desirably thelocal magnetic resonance frame of reference. The image desirably isderived in whole in part from the magnetic resonance informationobtained by use of the movable static field magnet and associatedcomponents. The aiming step may be performed at least in part byinspection of the image as, for example, by observation of arepresentation of the aim of the energy applicator superposed on theimage.

According to a further aspect of the invention, a method of treating amammalian subject may include the step of selecting a treatment volumewithin the subject having boundaries defined in a working frame ofreference.

A method according to this aspect of the invention may also include thesteps of actuating the applicator to apply energy at a plurality of testpoints in or adjacent the treatment volume and determining a degree ofheating of the tissue at each such test point resulting from suchactuation. Most preferably, the method further includes the step ofderiving a relationship between energy applied by the applicator anddegree of heating for a plurality of treatment locations within thetreatment volume from the degrees of heating of the test points and theenergy applied by the applicator to the test points. A method accordingto this aspect of the invention desirably further includes the step ofactuating the applicator to apply energy at the treatment locations, theamount of energy applied by the applicator in this step at each suchtreatment location being selected at least in part on the basis of therelationship between energy and heating for such treatment locationderived in the aforesaid steps. This method may be used in magneticresonance-guided hyperthermia including the aforesaid methods using themovable static field magnet, and other methods. The step of determiningdegrees of heating for the test points desirably includes the step ofacquiring magnetic resonance information for each such test point. Thetest doses of energy desirably are applied at levels less than athreshold level required to cause permanent change in the tissues at thetest points. The step of deriving the energy to heating relationship forthe treatment locations desirably includes the step of deriving arelationship between energy supplied and degree of heating for each testpoint and interpolating between such relationships over distance betweenthe test points. In a particularly preferred arrangement, the boundariesof the treatment volume include one or more polyhedral primitives andthe test points are disposed adjacent vertices of the polyhedralprimitives. The boundaries may be selected by displaying an image of thesubject in the working frame reference encompassing the region to betreated, displaying a visual representation of the boundaries superposedon the image and applying manual inputs to a control element to adjustthe boundaries while the visual representation is displayed.

After the boundaries have been established, some or all of the remainingsteps desirably are performed automatically. Thus, the step of actuatingthe applicator to apply the therapeutic energy at the treatmentlocations may be performed by automatically adjusting the aim of theapplicator to different treatment locations within the preset boundariesaccording to a preselected sequence such as a sequential raster scan ora pseudorandom pattern and automatically operating the applicator toapply the appropriate therapeutic dose. Methods according to this aspectof the present invention greatly facilitate the therapeutic process.They provide good control over the therapy and compensation for thevarying response to applied energy at different points within the bodywhile greatly minimizing the time spent in determining thesusceptibilities at various points and the effort required to performthe procedure.

Yet another aspect of the present invention provides a method of therapyincluding the steps of defining an avoidance zone encompassing thetissues of the subject which are not to be subjected to treatment in aworking frame of reference and recording the boundaries of the avoidancezone. A method according to this aspect of the invention also includesthe step of operating an intrabody treatment device such as an energyapplicator by manually moving an aim point of the treatment devicerelative to the subject and manually actuating the treatment device toapply a treatment at the aim point. Methods according to this aspect ofthe invention also include the step of tracking the aim point in theworking frame of reference during the manual operation step andautomatically controlling operation of the treatment device so as topreclude application of the treatment in the avoidance zone. The step ofautomatically controlling operation may include the step ofautomatically inhibiting movement of the aim point into the avoidancezone. For example, the step of manually moving the aim point may includethe step of manually moving an actuator such as a joystick and the stepof automatically inhibiting movement of the aim point may include thestep of providing force feedback opposing movement of the actuator in adirection corresponding to movement of the aim point into the avoidancezone when the aim point is near the avoidance zone. Alternatively oradditionally, the step of automatically controlling operation of thetreatment device may include the step of inhibiting application of thetreatment when the aim point is in the avoidance zone. For example,where the treatment device is an energy applicator, the automaticcontrol may inhibit application of energy if the aim point is in thepredefined avoidance zone. The avoidance zone may be defined in a mannersimilar to the treatment volume discussed above, i.e., by displaying avisual representation of the image of the subject and displaying avisual representation of the boundaries of the avoidance zone superposedon such image while applying manual inputs to a control element toadjust the boundaries. Methods according to this aspect of the presentinvention provide greatly enhanced safety in manually controlledtherapeutic procedures such as thermal ablation of tissues. These andother features and advantages of the present invention would be morereadily apparent from the detailed description of the preferredembodiments set forth below, taken in conjunction with the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective, partially block diagrammatic view depictingapparatus in accordance with one embodiment of the invention.

FIG. 2 is a diagrammatic perspective view depicting portions of a magnetincorporated in the apparatus of FIG. 1.

FIG. 3 is a diagrammatic view depicting still further portions of theapparatus of FIGS. 1 and 2.

FIG. 4 is a diagrammatic elevational view depicting gradient coilsemployed in the apparatus of FIGS. 1-4.

FIG. 5 is a diagrammatic sectional view depicting a high intensityfocused ultrasound unit and associate components used in the apparatusof FIGS. 1-4.

FIG. 6 is a diagrammatic sectional view depicting a portion of theultrasound unit shown in FIG. 5.

FIGS. 7 and 8 are diagrammatic representations of screen displays duringcertain methods in accordance with the invention.

FIG. 9 is a diagrammatic perspective view depicting gradient coils inaccordance with a further embodiment of the invention.

FIG. 10 is a diagrammatic elevational view depicting gradient coils ofFIG. 10 in conjunction with other elements of the apparatus.

FIG. 11 is a diagrammatic elevational view depicting gradient coils inaccordance with yet another embodiment of the invention.

FIG. 12 is a diagrammatic elevational view depicting apparatus inaccordance with yet another embodiment of the invention.

FIG. 13 is a diagrammatic perspective view depicting apparatus inaccordance with yet another embodiment of the invention.

FIG. 14 is a diagram depicting yet another embodiment of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Apparatus in accordance with one embodiment of the invention includes amobile unit 10 incorporating a static field magnet 12, gradient coilassembly 14 and a command and control console 13 all mounted to a commonchassis 15. The chassis 15 includes an arm 17 projecting upwardly fromthe other components and projecting in a forward direction indicated byarrow F in FIG. 1. A mounting socket 19 at the forward end of arm 17carries a disposable high-intensity focused ultrasound or “HIFU” emitter16. As further explained below, the static field magnet 12 is arrangedto provide a suitable magnetic field for magnetic resonance imagingwithin a magnetic resonance volume disposed forwardly of unit 10,whereas the HIFU unit 16 is arranged to apply ultrasonic energy atselected focal points within an energy application zone 21 intersectingmagnetic resonance volume 20. Chassis 15 is mounted on a positioningsystem 23. The positioning system 23 is supported on a base 25. Base 25in turn is provided with casters 27. Casters 27 can be extended so thatthe entire mobile unit 10 and base 25 can be moved across the floor ofthe room and can be brought into close alignment with a desired regionof a patient pier lying on a bed 24. Once the unit is roughly alignedwith the desired region, the casters may be retracted and the unit maybe brought into the desired, more precise alignment using thepositioning system 23 as discussed below. Casters 27 may be replaced byslides, air cushion supports. Positioning system 23 includesconventional devices such as hydraulic or pneumatic actuators, screwjacks and rotary movement devices for moving chassis 15 in multipledegrees of freedom including translation in all vertical and horizontaldirections and rotation about three orthogonal axes. Positioning system23 also includes conventional drive components such as servo motors fordriving mechanical linkages and pumps for driving hydraulic or pneumaticmovement devices. Moreover, the positioning system desirably includesconventional feedback control elements such as potentiometers andoptoelectronic encoders for providing signals indicating the relativepositions of the movable elements in the positioning system and therebyindicating the position and orientation of the chassis 15. For example,where transitional or pivoting movement of the chassis in one degree offreedom is controlled by a screw mechanism, the screw shaft may beprovided with a conventional digital encoder for detecting and reportingthe positions of the shaft. Control console 13 is linked to a controlcomputer 29. The control computer is also linked through a positionerinterface 31 to positioner 23. The positioner interface includesconventional components for converting signals sent by the feedbackcontrol components of the positioner into the digital format used by thecontrol computer, and for converting signals from the control computerinto driver signals for the positioning system. A static field actuationunit 33 controls the currents in the coils of the static field magnet12, whereas a gradient driver 35 actuates the gradient coils 14 toimpose magnetic field gradients as discussed below. A radio frequencyantenna 37 is mounted around the HIFU unit 16 and linked to an RFtransceiver 39. The transceiver 39 is also controlled by controlcomputer 29. Further, an electrical driver 41 is connected to HIFU unit16. Driver 41 is also controlled by control computer 29. As furtherdiscussed below, these components cooperate to perform magneticresonance imaging within magnetic resonance volume 20 and to applyultrasonic energy at selective points in energy application volume 21.

The Static Filed Magnet

As best seen in FIG. 2, static field magnet assembly 12 includes aplurality of cylindrical superconductive coils concentric with a centralaxis 26. The coils include an inner coil 28; middle coil 30; and outercoil 34 arranged concentrically with one another. A toroidal cryostat 36encloses these coils. As best seen in FIG. 1, cryostat 36 defines aninterior bore 38 extending through the innermost coil 28 andencompassing axis 26. Cryostat 36 is formed as a toroidal shell of anon-ferromagnetic material. The cryostat contains a coolant such asliquid helium or liquid nitrogen for maintaining the coils atsuperconducting temperatures. In a known manner, the coils are supportedwithin the cryostat by internal supports (not shown). Although the wallof the cryostat is illustrated as a simple wall, in actual practice thecryostat desirably has one or more multiple wall structures withevacuated spaces between the walls. Such a structure is also referred toas a Dewar vessel and minimizes heat conduction to the contents of thecryostat, including the coils and the coolant. Alternatively, thecryostat may be an insulated enclosure which is cooled by means otherthan cryogenic fluids, such as by thermoelectric cooling or otherconventional refrigeration systems. These systems can be used with highT_(c) superconductors.

The frame of reference and dimensioning system used to denote thedimensions of the individual coils are illustrated in FIG. 3. The meanradius or R_(m) and radial thickness T_(r) of each coil are specifiedwith respect to the central axis 26. The axial placement of each coil isgiven as the mean axial dimension A_(m) of the coil, measured from thecenter point 22 of the magnetic resonance volume. The axial thicknessT_(a) of each coil is the dimension of the coil parallel to axis 26. Thecoil also defines a frontal plane 40 perpendicular to axis 26 at theforwardmost extent of the forwardmost coil in the static field magnetassembly.

The coils of magnet 12 are connected to a conventional current source orstatic field actuator unit 33 (FIG. 1). Unit 33 provides currents in thecoils. The directions of current flow in the various coils are denotedas “positive” or “negative” “symbols” as indicated by the arrows in FIG.3. These arbitrarily-selected directions of current flow are opposite toone another. The forward spacing distance f or distance from the frontalplane of the static field magnet assembly to the center point 22 ofimaging volume 20 is also illustrated in FIG. 3.

The dimensions of the coils for the exemplary embodiment shown in FIGS.1, 2 and 3 are set forth in Table I below.

TABLE I Axial Thick Axial ness Mean Radial Current Ampere Location T_(a)Radius Thickness Coil Sense Turns A_(m) (cm) (cm) R_(m) (cm) T_(r) (cm)Inner Positive 1,159,200 33.7 14 17.88 5.04 (28) Middle Negative1,863,000 33.7 14 25.55 8.1 (30) Outer Positive 1,076,400 33.7 14 36.644.68 (34)

As indicated, the magnet provides a field of approximately 1 kilogausswith a relatively small linear axial field gradient $\frac{B}{Z}$

within a region about 5 cm in diameter at about 25-30 cm from thefrontal plane. In this same region, the radial field curvature$\frac{^{2}B}{X^{2}}$

is also relatively small and hence the field gradient in the radialdirection is also relatively small. The magnet provides a field with alinear axial gradient and with very small radial gradients over amagnetic resonance volume or imaging volume 20 having axial extent ofabout 1 cm and having a diameter of about 3 cm. The volume 26 centeredon point 22 at a forward spacing distance f from the frontal plane 40 ofabout 26 cm. The magnet is relatively small; the coils of the magnet canbe accommodated in a cylinder approximately 78 cm in diameter and onlyabout 14 cm thick. The small dimensions of the magnet dramaticallyreduce the cost and weight of the cryostat, and the cost of operation.Depending upon the materials used for the cryostat, the entire magnetmay have a mass of less than about 500 kg and hence can be moved andpositioned relative to the patient by a positioning device 23 ofreasonable size.

The Gradient Coil Assembly

The gradient coil assembly 14 is depicted in FIG. 4. The gradient coilassembly includes four windings 50, 52, 54 and 56 disposed around thecommon or central axis 26 of the static field magnet so that windings 50and 52 form one diametrically opposed pair of windings and windings 54and 56 form another diametrically opposed pair. The windings aregenerally planar and lie generally in plane perpendicular to the axis 26of the static field magnet. Coils 50 and 52 are disposed along a firstaxis (labeled “X” in FIG. 4) perpendicular to the central axis 26 orZ-direction of the static field magnet 12, whereas the other pair ofwindings 54 and 56 are disposed along another axis (labeled “Y” in FIG.4) perpendicular to the central axis 26 or Z-direction and perpendicularto the X axis of windings 50 and 52. The windings are formed frommetallic ribbon having a small thickness dimension and a larger widthdimension, the ribbon being wound on edge so that the width wisedirection of the ribbon extends perpendicular to the plane of thewinding and hence parallel to the axis 26. For example, the ribbon maybe about 0.016 inches (0.4 mm) thick and about 0.75 inches (2 cm) wide.Each winding may include about 120 turns of such ribbon. Winding 50includes an outer arcuate run 58 generally in the form of a circular arcconcentric with axis 26, and also includes a pair of radial runs 60 and62 extending generally radially inwardly from the ends of the arcuaterun 58. These runs merge with one another adjacent central axis 26. Eachof the other coils 52, 54 and 56 includes similar runs. Because thestatic field magnet inherently imposes a field gradient in the axial orZ direction, the gradient coil assembly used in this embodiment does notinclude a Z-direction gradient coil. However, if a Z-direction gradientcoil is required, the same may be as a circular solenoid concentric withcentral axis 26.

The windings are mounted in a non-ferromagnetic housing 57 which isprovided with cooling passages (not shown) connected to a chiller orother source of coolant. The radius from the central axis 26 to theoutside of the outer arcuate run of each winding desirably is about 25cm or less so that the entire gradient coil assembly 14 and housing 57is only about 50 cm diameter and about 3-4 cm thick.

Housing 57 is disposed immediately in front of the static field magnet12, i.e., just forward of the cryostat 36 and as close as possible tothe frontal plane 40 of the static field magnet. This leaves a largeunoccupied region along the axis 26 between the gradient coil assemblyand the imaging volume 20, so that the imaging volume can be positioneddeep within the patient's body. The windings of the gradient coilassembly are connected to gradient driver 35. The power and controlleads to the gradient coils may extend through the bore of cryostat 36.

The gradient driver includes conventional D/A converters and amplifiersfor receiving a desired gradient waveform in digital form from computer29, converting the digital waveform to analog form and reproducing theanalog waveform as currents in particular gradient coils controlled bythe computer of the apparatus. To apply a magnetic field gradient in theX-direction within the imaging volume 20, the two windings of a pair maybe energized so that the current flows in the outer arcuate runs of bothwindings in the opposite directions around the axis 26 of the staticmagnetic field assembly. For example, when windings 50 and 52 areenergized with the current flows as indicated by arrow C in FIG. 4, theywill provide a field gradient in one direction in the X axis. Thereverse current flows will produce a gradient in the opposite direction.Windings 54 and 56 can be actuated in the same manner so as to impose afield gradient in the Y-direction.

The HIFU Unit and RF System

The socket 19 at the forward or distal end of arm 17 includes amechanical mounting element 62 (FIG. 5) such as the tapered boreillustrated or any other conventional device for making a releasablemechanical interengagement. For example, the tapered bore 62 may bereplaced by a conventional vise, clamp, bolt joint or gripper, amulti-jawed chuck or a collet chuck. Mounting 19 also includes a coolantsupply passage 63 and coolant withdrawal passage 64 which are connectedto a conventional source (not shown) of a coolant such as chilled water.Mounting 19 further includes a multi-element electrical connector 66which in turn is connected to the high intensity focused ultrasounddriver 41 (FIG. 1).

The ultrasonic energy applicator 16 includes a disposable high intensityfocused ultrasound unit 68. Unit 68 includes a substantially rigid frame70, desirably formed from a polymeric material such as a polycarbonateor epoxy or other relatively rigid, high strength polymer. Frame 70 hasa mounting element 72 rigidly connected thereto. The mounting element 72is adapted to mate with the mounting receptacle 62 to form a rigid yetreleasable connection. For example, where the mounting receptacleincludes a tapered socket, mounting element 72 may be a pin having amating taper. Frame 70 defines a shallow dish generally in the form of asurface of revolution about an axis 74.

A plurality of ultrasound emitting sections 76 are disposed in a arrayon frame 70. As best seen in FIG. 6, each section 76 includes a rigidbacking 78 such as a block of alumina, glass or rigid polymer. Thesection also includes a piezoelectric film 80 such as a polyvinylidenefluoride film of the type sold under the registered trademark Kynar byAMP Inc. of Harrisburg, Pennsylvania. A set of rear electrodes 82 isprovided between film 80 and the backing 78, whereas a set of frontelectrodes 84 is provided on the front surface of film 80 facing awayfrom backing 78. The front and rear electrodes are provided in matchedpairs, so that the front electrode of each pair overlies the rearelectrode of each pair. For example, electrodes 82(a) and 84(a) form apair. These electrodes are aligned with one another and overlie with oneanother. Although only three pairs of electrodes are visible in FIG. 6,the emitter section 76 may include numerous pairs of electrodes arrangedin an array, as, for example, a three by three array incorporating ninepairs. A separate lead extends to each electrode. Electrodes 82 and 84desirably are formed as thin conductive deposits on the surfaces ofpiezoelectric film 80 as, for example, by applying an electricallyconductive ink on the surfaces of the piezoelectric layer or byprocesses such as sputtering or electroless plating, followed byelectroplating. Individual leads 86 extend from each of the electrodes.

Each pair of electrodes, and the portion of film 80 disposed betweensuch pair of electrodes films an independently operable piezoelectrictransducer. By applying opposite voltages to the two electrodes of thepair, the region of the film between the electrodes can be made toexpand or contract in the forward to rearward direction, i.e., in thedirection towards the top and the bottom of the drawing as seen in FIG.6. Thus, by applying an alternating potential, the portion of the filmbetween each pair of electrodes can be driven at ultrasonic frequencies.The particular section illustrated has the rear electrodes directlybonded to the surface of backing 78 so that the rear electrodes and therear surface of the film are held rigidly. In this arrangement, it isdesirable for the thickness of the film 80 to be approximatelyone-quarter of the wavelength of the ultrasonic vibrations. Typicaloperating frequencies are in a range of about 1 to 1.8 MHz, mostcommonly about 1.5 MHz, and the wavelength of the ultrasonic vibrationsin the film is about 1 mm. Thus, where the rear surface of film isrigidly held to the backing as in the embodiment of FIG. 6, thepreferred thickness of film 80 is about 250 microns. In otherembodiments, the film is supported away from the backing, so that therear surface of the film is spaced from the backing and is free tovibrate. In these embodiments, the thickness of the film isapproximately one half wavelength and desirably is about 500 microns ormore. Protective layers (not shown) such as a thin polymeric film orencapsulant may be provided over the front surfaces of film 80 andelectrodes 84 to protect them from contact with the environment. A ring90 formed from a rigid material such as alumina or polymeric materialextends around the periphery of the film. Ring 90 is secured to support78.

Sections 76 are secured to the frame 70 (FIG. 5). The individual leadsassociated with the various electrodes of all of the sections areconnected through a common cable 92 to a multi-element plug 94 adaptedto mate with multi-element socket 66 of mounting 19. The individualleads and cable 92 are constructed using standard techniques applicableto electrical structures for frequencies on the order of 1.5 MHz. Forexample, the individual leads to each pair of electrodes desirably areprovided as a coaxial, twisted pair or other transmission line suitablefor high frequency operation. Also, cable 92 may be formed as aso-called flex circuit capable of accommodating a large number oftransmission lines. The individual sections 76 are mounted in the frameso that the forward or active surface (the surface bearing forwardelectrodes 84) faces forwardly, i.e., in the downward direction as seenin FIG. 6. The front faces of the elements are directed generallyinwardly towards an applicator axis 74 as well as forwardly. Theindividual elements of the sections thus constitute a phased array ofultrasonic emitters. The energy emitted by the various ultrasonicemitters can be focused into a small focal spot 94. Desirably, the arrayis optimized to provide a spot having dimensions on the order of about2-3 mm. Where the device will be used for thermal ablation, the arraydesirably provides an ultrasonic intensity of approximately 1500watts/cm² at the focal spot to enable heating of tissues at the focalspot from about 37° C. to about 60-80° C. in less than one second. Suchrapid heating capability greatly reduces treatement time. Typically,approximately 1500 watts of electrical power must be applied to thearray to yield about 500 watts of ultrasonic emission. The focal spotcan be provided over a range of positions within energy applicationvolume 21. The focal spot can be moved within energy application volume21 by varying the phases and amplitudes of the driving signals appliedto the individual ultrasonic emitting elements, i.e., by varying thephases and amplitudes of the electrical signals sent to the variouselectrodes 82 and 84.

The size and shape of the focal spot, as well as the range of positionsover which the spot may be moved depends on the relative placement andproperties of the emitters. Desirably, the array is arranged to providea focal length of about 20 cm, i.e., the distance from the array to thecenter of the energy application volume 21 along axis 74 is about 20 cmor more. Typically, the array has a diameter of about 15 cm. Theparticular arrangement discussed above is merely exemplary. Thus, theindividual sections may be flat as discussed above, or else may becurved. Curved sections may have a generally spherical shapes, or elsemay may have different radii of curvature along differenct axes. Thesections may be smaller or larger than those discussed above. At oneextreme, each section may include only one element. At the otherextreme, the entire array can be formed as a single curved section andthe backing of such section can serve as the frame 70. The individualemitting elements within the array, and the individual emitting elementswithin a single section, may have different shapes and sizes. Forexample, the emitting elements may have square or other polygonalshapes, or may have circular or elliptical. The design of ultrasonicphased arrays, and computer simulations of such arrays are disclosed inEbbini, et al., Optimization of the Intensity Gain of Multiple-FocusedPhased Array Heating Patterns, Int. J. Hyperthermia, 1991, Vol. 7, #6,pp. 953-973; Ebbini et al., Multiple-Focused Ultrasound Phased-ArrayPattern Synthesis: Optimal Driving Signal Distributions forHyperthermia, IEEE Transactions on Ultrasonics, Ferro Electrics andFrequency Control, Vol. 36, pp. 540-548 (1989) and Fan et al., ControlOver the Necrosed Tissue Volume During Non-Invasive Ultrasound SurgeryUsing a 16-Element Phased Array, Medical Physics, Vol. 22 (#3), pp.297-305 (1995). The disclosures of these articles are herebyincorporated by reference herein.

The disposable unit 68 further includes a flexible water-filled bag 98attached to the frame 70 so that the ultrasonic emitting elements on theframe are coupled to the water for transmission of ultrasonic emissionsinto the water. For example, the bag may be attached to the periphery offrame 70. Bag 98 may be formed from a thin polymeric film. For example,the surface of the bag which will lie against the subject's body in usemay be formed from a polyethylene terepthalate film, whereas the otherwalls of the bag may be formed from a polyethylene film. Preferably, thewater within bag 98 is substantially free of dissolved air. If the filmconstituting bag 98 is air-permeable, it is preferably to remove airfrom the water during manufacture of the disposable unit, and to supplythe disposable unit vacuum-packed in an outer container which isair-impermeable. The disposable unit also includes a coolant passage 100having connectors 102 and 104 adapted to fit the coolant passages 63 and64 of mounting 19. The HIFU driver 41 (FIG. 1) includes conventionalcomponents for providing the required driving signals as commanded bycomputer 29. Driver 41 is connected to receptacle 66 so that when cable92 is connected to the receptacle, the HIFU driver is connected to allof the individual electrodes 82 and 84 of the piezoelectric elements.

A flexible skirt 106 is mounted permanently on the distal end of arm 17so that it surrounds mounting 19 and so that the skirt projectsdownwardly away from arm 17. The circular loop antenna 37 is mounted tothe edge of the skirt remote from the arm. RF transceiver 39 isconnected to loop antenna 37. The transceiver typically includes arelatively high powered transmitting section and a sensitive receiver,together with devices for disabling the receiver when the transmitter isactuated and vice versa. The RF antenna and transceiver desirably istunable over a range of frequencies corresponding to the range of Larmorfrequencies or magnetic resonance frequencies for protons subjected tothe magnetic fields of the static field magnet. Desirably, transmitterand receiver are provided with variable components such as variablecapacitors or capacitor switching networks for adjusting or tuning tomatch the Larmor frequencies at particular locations within the imagingvolume.

In use, the disposable HIFU unit 68 is received within skirt 106 andengaged with mounting 19 so that the HIFU unit is held physically on arm17 with the axis 74 of the HIFU unit projecting generally downwardly andhence transverse to the central axis 26 of the static field magnet. Inthis condition, the energy application volume 21 overlaps the imagingvolume 20. Moreover, the HIFU unit is rigidly held at a fixed positionand orientation with respect to the static field magnet. When the unitis operated with patient P, the arm 17 desirably is positioned so thatthe water bag 98 is engaged with the patient's skin. Ultrasonicvibrations may be transmitted from the piezoelectric elements of section76 through the water within a bag 98 and through the bag itself into thepatient with minimal losses. A gel or cream may be applied at thesurface of the bag to minimize transmission losses. Loop antenna 37 isdisposed in or near the patient's body surface. The axis of the loopantenna is close to or coincident with the axis 74 of the HIFU unit.Stated another way, the axis of loop antenna 108 is transverse to thecentral axis 26 of the static field magnet, and hence transverse to themagnetic field vector.

The Control Console and Control Computer

Control console 13 includes a conventional monitor 110 such as a cathoderay tube or flat panel display, as well as manual input devicesincluding a joystick 112 (FIG. 7) and a rotatable dial 114. Joystick 112desirably is a so-called “force-feedback” joystick, equipped withconventional devices for applying forces to the joystick responsive tocommands received by the joystick assembly. One suitable joystick issold under the trademark Sidewinder Force Feedback Pro by MicrosoftCorporation. Dial 114 may be incorporated in the joystick assembly. Thejoystick is also equipped with a push button 115.

The control console further includes additional command and controlswitches 116, and may further include a keyboard (not shown). All ofthese elements are linked to control computer 29. Control computer 29(FIG. 1) desirably is a conventional general purpose digital computersuch as a computer of the type commonly referred to as a “workstation”and includes conventional elements such as microprocessor and datatransfer bus (not shown). The control computer further includes memoryelements 118, which may incorporate conventional devices such as dynamicrandom access memory, flash memory or the like and mass storage such asmagnetic disc optional storage. The data bus of the control computer islinked through a conventional interfacing element (not shown) to theelements of the control console; to the positioner interface; to thestatic field application unit 33 and gradient driver 34 and to the HIFUdriver 41 and RF transceiver 39. The control computer program desirablyis arranged to display a menu of operating modes as discussed below onmonitor 110, so that the operator can select the desired operating modeby activating switches 116.

Operation

In a method according to an embodiment of the invention, a patient P(FIG. 1) is supported on a bed 24. Mobile unit 10 is moved on castors 27into a position such that the magnetic resonance volume 20 and energyapplication volume 21 are approximately aligned with the organ 120 ofthe patient which requires treatment. The water-filled bag of the HIFUunit is engaged with the patient's skin and the RF antenna 37 ispositioned around the bag. The operator actuates the computer to performa preliminary magnetic resonance imaging operation. Thus, the staticfield magnet is operated to apply the magnetic field within magneticresonance volume 20 and the gradient coils and RF transceiver areoperated to apply RF signals and magnetic field gradients in aconventional magnetic resonance imaging sequence. Transceiver 39 andantenna 37 are tuned to a frequency corresponding to the Larmorfrequency by atomic nuclei, preferably protons at the magnetic fieldprevailing in a particular thin slice S (FIG. 3) within magneticresonance volume 20. Because the magnetic field provided by the staticfield magnet incorporates a gradient in the axial or Z direction andbecause the Larmor frequency of the nuclei varies proportionally withthe prevailing magnetic field, the resonant or Larmor frequency varieswith distance along the Z axis. In the conventional manner, thetransceiver is actuated to send a pulse of RF energy into the subject,thereby exciting the nuclei within the slice S where the resonantfrequency of the nuclei matches the frequency of the RF signal. Also, ina conventional manner, the gradient coils are actuated to apply magneticfield gradients in the X and Y directions, transverse to the axial or Zdirection. This causes the signals from the nucleii at various positionswithin the slice to vary in frequency and phase in a known manner. TheRF transceiver is actuated to receive the magnetic resonance signals andto digitize the same and supply the digitized signals to controlcomputer 29. This process is repeated with variation of the X and Ygradients in known fashion. The signals acquired by transceiver 39 arestored in the memory of the computer. Using known procedures, thecontrol computer reconstructs an image of the subject's tissues withinslice S. This procedure can be repeated again using different radiofrequencies so as to select different slices within magnetic resonancevolume 20. The resulting data provides a three dimensional image of thatportion of the subject located within the magnetic resonance volume.

The image is displayed on monitor 110. The operator can observe theimage and determine whether the region of the subject to be treated iscentered in the field of view. As depicted in FIG. 7, the image may bedisplayed as a pair of orthogonal sectional views through the subject.If the region requiring treatment is not centered in the field of view,the operator can enter a command to the control computer, to enter arepositioning mode. In this mode, the computer accepts input from thejoystick 112 and dial 114. Thus, depending upon the commands receivedfrom the command input element 116, the control computer will interpretinput from joystick 112 and turn wheel 114 as commanding movement ofchassis 15 either in translation or in rotation. For example, thecomputer may be set to accept translation inputs and to treat joystickmovements in a direction X′ as commanding upward translation of thechassis; joystick movement in a direction Y′ as commanding horizontaltranslation and movement of turn wheel 114 as commanding forward andbackward or Z-direction translation of the chassis. After other commandsfrom command input element 116, the computer may treat joystickmovements in the X′ direction as commanding tilting movements about ahorizontal axis transverse to the central axis 26 and joystick movementsin the transverse direction Y′ as commanding rotation of the chassisaround a vertical axis. The imaging procedure is repeated, and theoperator continues to monitor the displayed images. As the operatorviews the images, he or she can use the images to diagnose conditionswithin the body as, for example, to detect lesions in the body whichrequire treatment. When the organ or region of the body which requirestreatment is centered in the field of view, the operator issues afurther signal to the command input element 116 which causes the controlcomputer to lock the position and thereby fix chassis 15, the staticfield magnet, the HIFU unit and other elements in position. Thus, thelocal magnetic resonance frame of reference established by the staticfield magnet and associated components is fixed.

In this condition, the computer treats inputs from joystick 112 and dial114 as commanding movement of a theoretical aim point in this fixedlocal magnetic frame of reference. Thus, as the joystick moves in X′ andY′ directions, the position of the theoretical aim point changes in theX and Y directions, respectively, whereas rotation of dial 114 causesmovement of the theoretical aim point in the Z direction. A cursor 124is displayed within the images on monitor 110 in a positioncorresponding to the position of the theoretical aim point. Using thedial and the joystick, the operator moves the cursor 124 to a series ofvertex points 126. The operator selects these vertex points so that theyconstitute to be vertexes of a polyhedron, or set of polyhedronsencompassing the treatment zone to be subjected to heating. In theexample illustrated in FIG. 8, the image shows a lesion L. The vertexpoints 126 are selected to form a pair of truncated pyramids 128 a and128 b which cooperatively encompass the lesion L. When the operatorbrings the cursor to each desired vertex, he issues a further command tothe control computer as, for example, by pressing a push button 130 onjoystick 112. The computer records the theoretical aim pointcorresponding to each such vertex in memory 118. The computer furthergenerates a wire-frame image of the polyhedron and vertex on displayscreen 110 and superposes this image over the image of the subject'stissues derived from the magnetic resonance information.

In the next stage of the process, the computer actuates the energyapplication or HIFU unit 16 to apply focused ultrasound at a spot 94 ata location corresponding to the location of one of the vertices 126. Thecomputer commands the HIFU driver to apply a relatively small“subthreshold” dose of energy to the tissues in the spot 94. That is,the amount of energy supplied by the HIFU driver is selected so that theheat applied in this operation will not destroy or alter the tissue. Forexample, in a human subject, the tissue may be heated from normal bodytemperature (37° C.) to about 40° C. In theory, because the HIFU unit isat a known location and orientation in the local magnetic frame ofreference, and because the location of spot 94 varies in a known mannerwith the signals supplied to the HIFU unit by HIFU driver 41, the heatedspot should be positioned exactly at the location commanded by computer29. In practice, due to inaccuracies in the equipment and refraction ofultrasonic energy by body structures, there will be some deviationbetween the position of the heated spot commanded by computer 29 and theactual position of the heated spot. After the subthreshold dose has beenapplied, the imaging procedure is repeated using a magnetic resonancesequence which is temperature sensitive, such as a T₁ weighted sequence,so that the displayed image includes a spot 94′ depicting the heatedspot. The operator then actuates the joystick 116 and dial 114 toposition cursor 124 over the spot 94 and provides a further controlinput for push button 115. The computer thus records the locationcorresponding to the position of the cursor as the position of theactual heated spot. The computer then subtracts the coordinates of theactual position from the corresponding coordinates of the commandedposition. The result is a correction vector. In the succeedingoperations, the computer will add this correction vector to all newcommanded positions so as to provide a corrected commanded positionwhich will result in heating at the true, commanded location.

Once the correction vector has been obtained, the computer executes atest point sequence. In the test point sequence, the computer commandsthe HIFU unit to apply a series of subthreshold doses at each vertex126, so that each vertex serves as a test point. When applying eachsubthreshold dose, the computer commands the HIFU unit to apply aparticular amount of energy to the heated spot of the vertex or testpoint. The magnetic resonance apparatus is actuated to determine thetemperature at each test point before and after application of eachsubthreshold dose. The computer records the amount of energy applied bythe HIFU unit (typically measured as input power supplied to the HIFUunit) and the resulting temperatures rise in memory 118. In this regard,the magnetic resonance imaging apparatus need not complete an entireimaging sequence to measure the temperature. Rather, the magneticresonance apparatus may be actuated in a known manner to acquiremagnetic resonance signals from a signal volume element or “voxel” atthe test point being heated. So-called “sensitive-point” magneticresonance methods are described in Mansfield and Morris, NMR Imaging inBiomedicine, 1982, p. 98. By monitoring a parameter of the magneticresonance signals which varies with the temperature of the tissues as,for example, the spinlattice relaxation time T₁, the computer canmonitor the temperature of the subject's tissues at the vertex or testpoint 126 being heated. From the recorded applied energies andtemperature increases, the computer calculates a calibration curve ofapplied energy versus temperature rise. In the simplest case, thecomputer calculates only the slopes of a linear plot of temperature riseversus applied energy.

Once the calibration curves have been obtained for all of the vertices,the operator actuates the computer to enter a treatment mode. Thecomputer commands the HIFU unit to apply energy to the subject's tissueswithin the treatment volumes or polyhedron 128. The computer commandsthe HIFU unit to apply a therapeutic dose sufficient to heat the tissueat each treatment location to a sufficient degree to perform therequired treatment. Where the treatment consists of thermal ablation,the treatment dose is selected to bring the temperature of the tissueabove about 43° C., and typically to about 60°-80° C. Other treatments,such as to enhance the effect of drugs or radiation therapy, typicallyuse lower temperatures. The amount of energy to be applied at eachtreatment location is selected based on an interpolated calibrationcurve. Thus, the calibration curve for each treatment location iscomputed by linear interpolation among the calibration curves for thetest point vertices of the polyhedral treatment volume. For example, thecomputer can calculate the distance between each treatment location andthe various vertices of the polyhedron encompassing that treatmentlocation and then calcute a weighted average slope S_(ave) according tothe formula$S_{ave} = \frac{\sum\limits_{i = 1}^{i = n}\quad \frac{S_{i}}{d_{i}}}{\sum\limits_{i = 1}^{i = n}\quad \frac{1}{d_{i}}}$

where:

S_(i) is the slope at the i^(th) vertex or test point; and

d_(i) is the distance from the treatment location to the i^(th) vertexor test point.

In the case where the treatment location overlies one test point so thatone distance d_(i) is zero, the computer sets S_(ave) equal to the slopeat that test point or vertex. For example, treatment location 136 a isclose to test point or vertex 126 a and far from test point or vertex126 b. The computer will set the slope of the energy versus temperaturerise plot at treatment location 136 a close to the slope at test point126 a. The computer automatically selects new treatment locations,calculates the slope at the newly selected treatment location andapplies the appropriate therapeutic dose until therapeutic doses havebeen applied at all possible treatment locations within the treatmentvolume defined by polyhedron 128 a and 128 b. Desirably, each treatmentlocation is brought to the desired temperature rapidly, typically in onesecond or less. Thus, the system can complete the treatment throughoutthe treatment volume rapidly.

During application of the therapeutic doses, the computer mayperiodically acquire magnetic resonance information from one or morevoxels within the treatment volume and monitor the temperature in suchvoxel based on this magnetic resonance information. Alternatively, thecomputer can actuate the magnetic resonance apparatus to conduct a fullmagnetic resonance imaging sequence using a temperature-sensitiveimaging protocol and display an image showing the heated region and thesurrounding tissues. The operator may command the system to acquire anew magnetic resonance image after completion of the entire treatment sothat the effect of the treatment can be assessed.

In an alternate procedure, the operator moves the theoretical aim pointapplicator using the joystick 112 and dial 114 so as to move the cursor124 (FIG. 8) about in the displayed image in the manner discussed above,and actuates button 115 to mark vertices 126′. However, the computer isinstructed to record these vertices as vertexes of an avoidance zonerather than as vertexes of the treatment volume. In the same manner asdescribed above, the computer generates a wire frame image of polyhedra128′ with vertexes corresponding to vertexes 126′. The operator selectsvertices 126′ and thus selects the tissues encompassed by the avoidancezone by observing the displayed image. In the example illustrated inFIG. 9, the image of a sensitive structure such as the urethra U isshown on the display monitor 110. The operator has established theavoidance zone so as to encompass the urethra. The computer records theboundaries of these polyhedra as boundaries of the avoidance zone. Theoperator manually selects test points 129 outside of the avoidance zoneand performs the calibrations step discussed above, so as to calibratethe system for errors in aim of the HIFU unit and to arrive at a applieddose to heating calibration curve for each test point 129. Once again,the test points desirably are selected so that they are at or near theperiphery of the lesion L′ to be treated.

The operator then commands to enter a manual ablation mode. In thismode, the computer responds to a manual operation of the joystick 112and dial 114 as commands to move the aim point of the HIFU unit, and thecomputer responds to manual actuation of the push button on the joystickas a command to apply a therapeutic dose at the current aim point. Forexample, with cursor 124 positioned over the image of lesion L′, thetheoretical aim point is within the lesion. Application of a therapeuticdose will heat the tissues at the point within the subject's bodycorresponding to the aim point. The dose can be selected automaticallybased upon the dose to heating calibration curves calculated asaforesaid or can be selected manually. If the operator attempts to movethe aim point into the avoidance zone, the system will prevent him fromdoing so. Thus, if the aim point is close to the avoidance zone, and ifthe operator commands the system to move the aim point into theavoidance zone, the system will not do so. Instead, the system willissue a warning signal by providing force feedback through the control.For example, with the cursor in the position indicated at 124′ in FIG.8, upward movement in the X direction will bring the cursor into theavoidance zone. If the operator attempts to move the joystick 112upwardly in the X′ direction and thus moves the cursor 124′ upwardly,the system will apply a countervailing force feedback to resist thismotion. Force feedback provides a uniquely intuitive warning to theoperator. However, other forms of warning signals may be employed. Forexample, the system may display an alphanumeric warning on the monitor110, or may cause the monitor display to flash or may illuminate thecursor in a distinct color. Audible warnings may also be employed.

In a further variant of this system, the computer allows the operator tomove the aim point into the avoidance zone, but inhibits application ofa therapeutic dose while the aim point is within the avoidance zone.Here again, the system can display any form of tactile visual or audiblewarning before the operator attempts to apply a therapeutic dose whilethe aim point is in the avoidance zone.

In the methods discussed above, the magnetic resonance information wasacquired in only a single magnetic resonance volume. However, the systemcan collect magnetic resonance information over a plurality of differentmagnetic resonance volumes. For example, as shown in FIG. 3 the staticfield magnets and related components can be swung about a vertical axisso as to swing the central axis 26′ to a new orientation and move themagnetic resonance volume to a new position indicated in broken lines at20′. Thus, a different local magnetic resonance frame of reference isestablished by moving the chassis and the static field magnets andrelated components mounted thereto. The computer records movement of thechassis between positions. Therefore, each new local magnetic resonanceframe of reference is in a known position and orientation relative toall of the preceding local magnetic resonance frames of reference.Magnetic resonance information gathered in all of the various frames ofreference can be transformed into a single, common working frame ofreference. In this manner, the system can display an image of thesubject encompassing features in a relatively large region. Because theHIFU unit 16 is mounted on the same chassis as the static field magnet,the frame of reference of the HIFU unit remains fixed with respect tothe frame of reference of the static field magnet. Thus, the system canbe operated to treat the subject while the chassis is in one positionand then moved to a new position to perform additional treatments ontissues at other locations within the subject's body. In effect, thecomputer constructs a mosaic of the relatively small magnetic resonanceimages so that the mosaic as a whole encompasses a large region of thesubject.

The gradient coils may have shapes other than the shapes discussed abovewith reference to FIG. 4. For example, the X and Y gradient coils may becircular. Also, where the static field magnet does not inherentlyprovide a field gradient in the axial or Z direction, a further coil orcoils may be provided. For example, the Z gradient coil may include acircular solenoid coaxial with the central axis of the static fieldmagnet.

In a further alternative embodiment, the X-gradient coils may be formedas a pair of opposed saddle-shaped coils 202 (FIGS. 9 and 10) arrangedon opposite sides of the central axis 226 of the static field magnet. Asbest seen in FIG. 10, each X-gradient coil 202 has elongated runs 203extending generally codirectionally with the central axis, and arcuateruns 205 extending partially around the central axis. The arcuate runsare spaced apart from one another in the direction along the X axis ofthe magnetic resonance frame of reference. As seen in FIG. 9, thegradient coil assembly may include a similar pair of saddle-shaped coils204 spaced apart from one another in the Y direction. The arcuate runsof the X and Y gradient coils at the forward ends of the coils aredisposed forwardly of the cryostat, whereas the elongated straight runsmay extend rearwardly through the central bore of the cryostat. The Xand Y gradient coils partially overlap one another as seen in end viewalong the central axis 226. In a further variant, the elongated runs ofthe saddle-shaped coils may extend on the outside of the cryostat.

In a further variant the X-direction gradient coils 210 (FIG. 11) areelongated in the Y direction, so that these coils can impose an Xdirection gradient throughout an elongated imaging region having arelatively large dimension in the Y direction. The Y-direction gradientcoils 212 are spaced relatively far apart, so that these coils can alsoapply the Y direction gradient over the same elongated imaging region.The gradient coils may be of different sizes. For example, theX-direction gradient coils 212 may be of different dimensions.

In place of the phased array HIFU units discussed above, the HIFU unitmay have a fixed focus, and the arm 17 or mounting 19 (FIG. 1) may bemay be articulated so that the focus of the ultrasound can be moved byturning the axis 74 of the HIFU unit 16 or moving the HIFU unit relativeto the chassis 15. In a further variant, an articulated arm 17′ ormounting 19′ supporting the HIFU unit 16′ (FIG. 12) can be combined withthe phased array. The articulated arm 17′ has a positioning device 23′associated with is so that the position and orientation of the HIFU unit16′ relative to chassis 15′ can be varied. However, the position andorientation of the HIFU unit 16′ in the local magnetic frame ofreference defined by the static field magnet remain known. This approachallows the operator to direct the ultrasonic energy into the subject'sbody from various directions, as at positions 16″ and 16′″, so as toavoid interfering body structures. The control computer can display amarker on the image of the subject which indicates the location of thecenter of the energy application zone 21′, so that the operator can movethe energy application zone to the desired position.

In a further variant, the ultrasonic transducers may be mounted on adeformable resilient flange and the flange may be selectively deformedby an actuator to vary the focus of the ultrasonic transducers and thusadjust the focus to the desired location. Alternatively, each transducercan be pivotally mounted on the instrument frame, and the pivotalmountings can be linked to one another so that the transducers pivottowards and away from the axis of the HIFU unit in unison. In a furtheralternative embodiment the HIFU unit may include ultrasonic transducersdisposed in an array coaxial with the central axis of the static fieldmagnet, such as an annular arrangement around the forward side of themagnet assembly. In such an arrangement, the ultrasonic axis is coaxialwith of the central axis of the magnet. Here again, the ultrasonictransducers may be mounted on a deformable flange or movable element sothat the focus of the ultrasonic energy can be adjusted.

In further variants, the ultrasonic transducers or HIFU unit can bereplaced by other devices for applying energy so as to heat tissue at aspot within the body. For example, a system for applying focusedradiofrequency (RF) energy can be utilized. The RF system can be mountedon the along with the magnetic resonance components. In a furthervariant, the focused RF energy may be provided by the same transmitterand antenna used for magnetic resonance operations.

In the arrangements discussed above, the energy applying device moveswith the magnet relative to the patient as the positioning system movesthe instrument chassis. In an alternative arrangement (FIG. 13) anenergy applying device 316 is mounted on one positioning system 318whereas the magnetic resonance apparatus 312, including the static fieldmagnet, is mounted on a separate positioning system 323. Both of thesepositioning systems are supported by rails 325 mounted overhead, so thatthe operator can move the components within the room. In use of thisapparatus, the energy applying device is positioned relative to thesubject in a separate step from the step of positioning of the magneticresonance device. Here again, however, the energy applying device ispositioned so that it can heat tissues in an energy application zone 321within the field of view of the magnetic resonance device, and inalignment with the body structure to be treated. The magnetic resonancedevice may be used to aid this positioning if the heating device isactuated during the positioning stage, so that the spot heated by theheating device can be located in the magnetic resonance image orotherwise detected by the magnetic resonance device. Alternatively, thecomputer may be arranged to display an indication of the center point ofthe energy application zone superposed on the image of the subject. Theactuation used during the positioning step preferably consists ofsubthreshold doses which heat the tissue only slightly, and does notpermanently damage the tissue.

Preferably, positioning systems 323 and 318 are arranged to track theposition and orientation of the magnetic resonance apparatus 312 andenergy applicator 316 in a common frame of reference, such as in theframe of reference of rails 325. The steps of positioning of themagnetic resonance apparatus 312 and the energy applicator 316 inalignment with one another, with energy application zone 321intersecting magnetic resonance volume 320 can be performed partially orentirely with based on data supplied by the positioning systems.

Using known techniques in the position sensing arts, the positioningsystem or systems may be registered with fiducial markers or anatomicallandmarks on the patient, and may be registered with previously-acquiredimage data, such as MRI or CT data defining a three-dimensional image ofthe subject. For example, a probe 330 may be connected to a positiondetector 332 adapted to provide the position of the probe tip in theframe of reference of magnetic resonance device 312 (the local magneticframe of reference), or in another frame of reference having a knownrelationship to the local magnetic frame of reference. Thepreviously-acquired image data includes images 332′ of identifiablepoints 332 on the subject's body, which may be naturally-occurringanatomical features such as prominent bony protruberances or fiducialmarkers attached to the subject before acquisition of the image data. Bytouching the tip of probe 330 to identifiable points 332, the operatorinputs the locations of these points in the local magnetic frame ofreference to the control computer. By manipulating a cursor on a monitordisplaying the previously-acquired image until the cursor is alignedwith the identifiable points, the operator inputs the locations of thesepoints in the frame of reference of the previously-acquired image data.Once the computer has the locations of the same points in both frames ofreference, it can derive the transform between the two frames ofreference using known techniques.

Once the transform is known, the previously-acquired image data can beused to supplement the data acquired by the magnetic resonance unit 312.For example, during the step of positioning the magnetic resonance andheating devices, representations of the aim points of these devices canbe depicted on a display showing the previously acquired image, andthese can be moved by moving the devices relative to the patient untilthe aim points are depicted as aligned on the region to be treated. Thesame approach can be used to align a single instrument incorporatingboth MR and heating capabilities.

In a variant of this approach, the movable magnetic resonance device isnot used to acquire an image of the subject. Rather, the movablemagnetic resonance device is used to acquire magnetic resonance dataonly in a single voxel at a known location in the local magneticresonance frame of reference so as to monitor the heating process. Thus,the movable magnetic resonance apparatus may be used to monitortemperature in a single voxel aligned with the focal spot of theenergy-applying device, during application of test doses or duringapplication of therapeutic doses. The operations discussed above, suchas defining treatment volumes or avoidance zones, may be performed insubstantially the same manner; the image displayed to the operator isbased on the previously-acquired image data. If the movable magneticresonance device is not used for imaging, magnet requirements such asfield uniformity and gradient linearity can be relaxed considerably,which in turn allows significant reductions in the size and cost of theapparatus. This approach depends upon the subject remaining in fixedposition during the treatment. In a variant of this approach, a markeron the subject may be tracked so as to track and compensate for movementof the subject. Such a marker and compensation scheme also may be usedwhere the movable magnetic resonance device is used to acquire images.

In the preferred embodiments discussed above, the magnet of the magneticresonance apparatus is a single-sided, movable magnet. Other movablemagnets can be used. For example, certain movable superconductingmagnets have been used for magnetic resonance imaging. These magnetshave dual coils mounted to a movable frame, so that the subject isdisposed between the coils. Also, aspects of the invention such as theuse of test points, treatment volumes and avoidance zones can bepracticed even when the procedure is conducted within a conventionalfixed magnetic resonance magnet.

In the embodiments discussed above, the focal spot of the HIFU unit orother energy applicator may be made as small as possible so that thetreatment can be precisely applied. In a method according to a furtherembodiment of the invention, the energy applying device is still focusedon a relatively small focal spot. However, the focal spot is swept overa larger “pseudo-focal region” (hereinafter “PFR”) while applyingenergy. The PFR typically is of larger size than the focal region. Forexample, the PFR may have dimensions on the order of 1 cm or so. Thesweeping process is performed so as to heat the entire PFR, or a portionof the PFR, to or above the desired temperature. Most preferably, thatportion of the PFR which reaches the desired temperature reaches suchtemperature at about the same time. In the sweeping process, the focalspot moves throughout the PFR either in a repetitive pattern or in apseudorandom pattern so as to heat different locations in the PFR atsuccessive times. The locations heated at successive times need not becontiguous or even adjacent to one another. Thus, the focal spot mayskip from location to location within the PFR, so that the focal spot islocated at widely-separated points within the PFR at successive times.For example, the focal spot may be moved in a raster-like pattern 404throughout a PFR 402 a so that neighboring points are heated atsuccessive times.

The average power applied to each point within the PFR may be controlledby controlling the duty cycle at each location. As used in connectionwith the pseudofocal region, the term “duty cycle” refers to theproportion of the entire heating time for the PFR that the energy isapplied to at the particular point. For example, if energy is applied tothe PFR by sweeping a focal region throughout the PFR for a period offive minutes, and the focal spot encompasses a particular location for atotal of five seconds during that five minute period, then the dutycycle at that spot is {fraction (1/60)} or about 1.6%. The duty cycleneed not by uniform within the PFR. For example, where a spherical PFRis to be heated to above the threshold temperature uniformly, so thatall portions of the PFR reach the threshold temperature at about thesame time, the center of the PFR may be treated with a lower duty cyclethan the outer portions of the PFR so as to compensate for the morerapid heat loss from the outer portions to the surrounding tissues. Forexample, the duty cycle at location 406 b may be lower than the dutycycle at location 406 a. Alternatively or additionally, the average rateof power application to various points within the PFR can be madenon-uniform by varying the power applied to the focal spot so that thepower level is different for different locations of the focal spotwithin the PFR. Moreover, the size of the focal spot can be varied, byadjusting the HIFU unit or other energy-applying device, so as to varythe power density (watts/cm³ of tissue within the focal spot) as thefocal region moves.

A PFR may have a wide variety of shapes as, for example, spherical,elliptical, rod-like, generally rectangular or the like. Typically theshape of the PFR is selected so that the PFR is a “simply-connected”region. As used herein, the term “simply-connected” refers to a regionsuch that, for any two points within the region, a straight lineconnecting the two points will be disposed entirely within the region.The aforementioned shapes are simply connected. By contrast, a toroid isnot simply-connected.

The energy input throughout the PFR can be calculated by monitoring thetemperature at various locations within the PFR as, for example, bymagnetic resonance temperature measurements at a point or points withina PFR or, alternatively, by capturing a continuous MRI map or image,which may be visually displayed. Using information obtained during theheating cycle, the heating process can be controlled manually orautomatically so as to vary the amount of energy input to variousregions of the PFR and terminate the heating process when the desiredthreshold temperature is reached in all regions of the PFR. The heatingprocess can be terminated selectively in different regions of the PFR aseach region reaches the desired temperature. For example, where thedesired temperature is a threshold temperature sufficient to kill thetissue, the heating process is terminated as each region of the PFRreaches the threshold temperature. Alternatively or additionally, theheating process can be controlled by prediction using test points in themanner discussed above.

The position of the PFR can be controlled in substantially the same wayas discussed above for control of the focal spot. For example, in acomputer controlled system where the computer prevents ablation of anavoidance zone containing sensitive anatomical structures, the computercan be controlled to inhibit energy application to any PFR whichoverlaps with the avoidance regions. Also, in a system as discussedabove with reference to FIG. 7, where the user supplies geometricalcoordinates for the volume to be treated, the operator controlling theprocess, or the computer, may select one or more PFRs having shapeswhich fit well with the regions to be ablated. For example, as shown inFIG. 14, the operator has defined an a treatment volume 400 encompassingthe region of the subject to be treated. The operator can then define aset of PFRs 402 which fill the treatment volume. The operator can enterthe boundaries of the PFRs into the computer in the same manner as theoperator enters the boundaries of the treatment volume. The computerthen actuates the energy applicator to heat each PFR.

As these and other variations and combinations of the features discussedabove can be utilized without departing from the present invention, theforegoing description of the preferred embodiments should be taken byway of illustration rather than by way of limitation of the invention asdefined by the claims.

What is claimed is:
 1. A high intensity focused ultrasound applicatorcomprising a frame, a plurality of ultrasonic emitters mounted on saidframe, and a bag containing a substantially air-free fluid permanentlyconnected to said frame so that said frame, said bag, said fluid andsaid emitters constitute a permanently-connected unit, said bagprojecting from said frame, said bag being flexible so that said bag iscapable of conforming to and engaging a surface of a patient's body,said emitters being coupled to said fluid for transmission of ultrasonicvibrations through said fluid, said unit being adapted for releasableconnection to an ultrasonic actuation apparatus.
 2. An applicator asclaimed in claim 1 wherein said fluid includes water.
 3. An applicatoras claimed in claim 1 wherein said ultrasonic emitters are piezoelectricelements.
 4. An applicator as claimed in claim 3 wherein saidpiezoelectric elements are provided in at least one section, each suchsection including a polymeric film and at least one pair of electrodesdisposed on opposite sides of the polymeric film.
 5. An applicator asclaimed in claim 4 wherein each said section includes a plurality ofpairs of electrodes overlying different regions of the film included inthat section.
 6. A hight intensity focused ultrasound applicatorcomprising a frame, a plurality of ultrasonic emitters mounted on saidframe, and a flexible bag containing a substantially air-free fluidpermanently connected to said frame so that said frame, said bag, saidfluid and said emitters constitute a permanently-connected unit, saidemitters being coupled to said fluid for transmission of ultrasonicvibrations through said fluid, said unit being adapted for releasableconnection to an ultrasonic actuation apparatus, the applicator furthercomprising a sealed air-impermeable package surrounding the frame andbag.
 7. A high intensity focused ultrasound applicator comprising aframe, a plurality of ultrasonic emitters mounted on said frame, and aflexible bag containing a substantially air-free fluid permanentlyconnected to said frame so that said frame, said bag, said fluid andsaid emitters constitute a permanently-connected unit, said emittersbeing coupled to said fluid for transmission of ultrasonic vibrationsthrough said fluid, said unit being adapted for releasable connection toan ultrasonic actuation apparatus, the applicator further comprising anair-impermeable package surrounding the frame and bag, said frame andbag being vacuum-packed within said air-impermeable package.